Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 39; p. 24022
Main Authors: Feng, Guoping, Jensen, Frances E, Greely, Henry T, Okano, Hideyuki, Treue, Stefan, Roberts, Angela C, Fox, James G, Caddick, Sarah, Poo, Mu-Ming, Newsome, William T, Morrison, John H
Format: Journal Article
Language:English
Published: United States 29.09.2020
Subjects:
Animal Experimentation - ethics
Animals
Disease Models, Animal
Mental Disorders - genetics
Mental Disorders - physiopathology
Nervous System Diseases - genetics
Nervous System Diseases - physiopathology
Neurosciences - ethics
Neurosciences - methods
Primates - genetics
Primates - physiology
CRISPR
nonhuman primate
primates
disease models
genetic engineering
ISSN:1091-6490, 1091-6490
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Summary:The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.2006515117